Chemotherapy is the use of drugs for treating a disease such as cancer. The drugs can be swallowed as pills, or they can be injected by needle into a vein or muscle. These drugs enter the bloodstream and reach most areas of the body; and are considered systemic treatment. This type of treatment is useful for diseases such as MDS that are not localized to one part of the body. The purpose of the chemotherapy is to eliminate the abnormal stem cells and allow normal ones to grow back.

Conventional chemotherapy

Because MDS can progress to acute leukemia, patients may receive the same treatment. Chemotherapy drugs often used for MDs and acute myeloid leukemia include cytarabine with idarubicin, cytarabine with topotecan, and cytarabine with fludarabine. This type of treatment can help some patients, but it has many severe side effects. Complications from chemotherapy may hasten death, particularly in the elderly. Still, this treatment may be an option for some patients with advanced MDS.

Another option is to use lower doses of chemotherapy drugs. This approach can lower the chance of serious side effects.

Chemotherapy drugs can cause many side effects. The side effects depend on the type and dose of the drugs that are given and how long they are taken. Common side effects include:

• hair loss
• mouth sores
• loss of appetite
• nausea and vomiting
• low blood counts

Chemotherapy often slows blood production, leading to low blood counts. In MDS, this problem is usually made worse before it gets better. It can lead to lowered resistance to infection (due to low white blood cell counts), easy bruising and bleeding (due to low platelet counts), and fatigue (due to low red blood cell counts).

At times during treatment when their white blood cell counts are very low, patients can reduce their risk of infection by avoiding exposure to bacteria, fungi, or viruses. Wearing a surgical mask around crowds and construction areas is often recommended. During this time, patients should be very careful about washing hands and avoiding fresh, uncooked fruit and other foods that might carry germs. Another important way to protect patients with low white blood cell counts against infection is treatment with powerful antibiotics. These may be given before signs of infection or at the earliest sign that an infection may be developing.

While their platelet counts are low, patients may receive platelet transfusions as protection against bleeding. Likewise, fatigue caused by low red blood cell counts can be treated with red blood cell transfusions.

Most side effects are temporary and will go away after treatment is finished. Your health care team often can suggest ways to lessen side effects. For example, other drugs can be given along with the chemotherapy to prevent or reduce nausea and vomiting.

Chemotherapy drugs can also damage organs such as the kidneys, liver, testicles, ovaries, brain, heart, and lungs. With careful monitoring, such side effects are rare. If serious side effects occur, the chemotherapy treatments may have to be reduced or stopped, at least temporarily.

Carefully monitoring and adjusting drug doses are important because some of these side effects can be permanent.

Hypomethylating agents

These drugs are actually a form of chemotherapy that affect the way genes are controlled. They help in MDS by slowing down genes that promote cell growth. They also kill cells that are dividing rapidly. Examples of this type of drug include azacytidine (Vidaza) and decitabine (Dacogen). In some MDS patients, these drugs improve blood counts, lower the chance of getting leukemia, and even prolong life. Red blood cell counts may improve enough to stop transfusions.

These drugs have some of the same side effects as regular chemotherapy, including:

• nausea/vomiting
• diarrhea or constipation
• fatigue and weakness
• low blood counts (most often the white blood cells or platelets)

Immune treatments

Immune modulating drugs: The drugs thalidomide and lenalidomide (Revlimid) belong to the class of drugs known as immunomodulating drugs (or IMiDs). Thalidomide was used first in treating MDS. It helped some patients, but many people stopped taking the drug because of side effects. Lenalidomide is a newer drug related to thalidomide that has fewer side effects. It seems to work well in low-grade MDS, eliminating the need for transfusions in about half the patients treated. The drug seems to work best in people whose MDS cells are missing a part of chromosome number 5 (this is called del(5q) or 5q-) and is approved by the FDA approval to treat these patients. It can also help other MDS patients.

Side effects include:

• decreased blood counts (most often the white cell count and platelet count)
• diarrhea or constipation
• fatigue and weakness

Lenalidomide can also increase the risk of serious blood clots that start in the veins in the legs (called deep venous thrombosis or DVT). Part of a DVT can break off and travel to the lungs (called a pulmonary embolus or PE), where it can cause problems with breathing or even death. Many experts feel that patients getting this drug should also get some kind of treatment to prevent blood clots.

When thalidomide was first released in the 1960s, it was found to cause serious birth defects if given to pregnant women. This led to the drug being taken off the market for many years. Now, it is only available through a special program of the drug company. Although lenalidomide hasn't been shown to cause birth defects, concern about this risk has limited the availability of this drug as well. It is also only available through a program from the company that makes it.

Immunosuppression: Drugs that suppress the immune system can help some patients with MDS. These drugs are used more often in patients with aplastic anemia, a condition where the immune system attacks the bone marrow, leading to low blood counts.

A drug called anti-thymocyte globulin (ATG) has helped some people, usually younger ones, with MDS. The drug is an antibody against a type of white blood cell called the T-lymphocyte. T-lymphocytes help control immune reactions. In some patients with MDS, T-lymphocytes interfere with normal blood cell production. ATG is given as an infusion through a vein. It must be given in the hospital because it can sometimes cause severe allergic reactions leading to low blood pressure and problems breathing.

Another drug that works by suppressing the immune system is called cyclosporine. It was first used to block immune responses in people who have had organ or bone marrow transplants, but, it has helped some patients with MDS. Side effects of cyclosporine include loss of appetite and kidney damage.